Paclitaxel (II) is a naturally occurring diterpenoid taxane present at low concentration in several species of the slow-growing yew tree (Taxus genus, Taxaceae family), which has been approved for the treatment of refractory advanced ovarian cancer, breast cancer and Kaposi's sarcoma.

Docetaxel (III) is a synthetic diterpenoid taxane which has been approved for the treatment of breast cancer, locally advanced or metastatic non-small cell lung cancer (in combination with cisplatin) and prostate cancer (in combination with prednisone).

Due to the complex structure of the taxane nucleus, total synthesis of paclitaxel and docetaxel is very long and expensive, therefore it is not suitable for an industrial scale. So far, large-scale preparation of these compounds has been accomplished by semi-synthesis from appropriate starting materials, such as 10-deacetylbaccatine III (IV) (herein after referred to as 10-DAB III)

a biogenetic precursor of paclitaxel, and an enantiomerically pure precursor of the 3-phenyl-isoserinyl side-chain at C-13. US 2005/0049297, in the Applicant's name, discloses the reaction between 10-DAB protected at position 7 with a compound of formula (V)

which is in turn prepared from (2R,3S)-3-phenylisoserine methyl ester acetate salt (I)

Compound (V) contains an easily removable nitrogen protecting group (the 2-nitrophenylsulfanyl moiety) and can therefore be used for the synthesis of both paclitaxel and docetaxel, which is indeed convenient from the industrial standpoint.
Methods for the synthesis of enantiomerically pure (2R,3S)-3-phenylisoserine methyl ester are reported in the literature.
Natural Product Letters vol. 6, pp. 147-152 discloses the reaction of benzaldehyde and chloroacetic acid methyl ester in the presence of sodium methoxide to give racemic trans 3-phenylglicidic acid methyl ester, which is converted to the racemic cis isomer via epoxide ring opening with gaseous HCl in benzene and subsequent epoxide closure by treatment with Amberlite 400 (OH−). The racemic cis-epoxide is then treated with KOH in ethanol to give the potassium salt which is added with HCl to liberate racemic cis-phenylglicidic acid. Treatment with D-(+)-ephedrine provides a mixture of diastereomeric salts, wherefrom cis-(2R,3S)-3-phenylglicidic acid (+)- ephedrine salt can be recovered in 30% yield by fractional crystallisation with acetone. Acidic treatment of the ephedrine salt allows to obtain optically active phenylglycidic acid, which can be treated with ammonia to provide (2R,3S)-3-phenylisoserine acid. The scaling-up of this process is troublesome because, as also reported by the authors, cis-phenylglycidic acid is unstable and its optical resolution is successful only if carried out rapidly, which is generally very difficult to achieve on an industrial scale.
Synthetic Communications, 31 (23), 3609-3615 (2001) discloses a similar procedure for the obtainment of racemic cis-3-phenylglycidic methyl ester. Thereafter, the method comprises the treatment of racemic cis-3-phenylglycidic acid methyl ester with ammonia to obtain racemic threo-3-phenylisoserine amide, which is hydrolysed with barium hydroxide to racemic threo-3-phenylisoserine acid and benzoylated to give racemic threo-N-benzoyl-3-phenylisoserine acid. The racemic mixture is resolved by fractional crystallisation with S-(−)-methylbenzylamine to give (2R,3S)-N-benzoyl-3-phenylisoserine acid. This compound is not suitable for the production of (2R,3S)-3-phenylisoserine methyl ester (I), because the removal of the benzoyl group requires harsh conditions (i.e. 6 N HCl, reflux, 48 hours) and may affect the stereochemistry of the molecule.
In U.S. Pat. No. 6,025,516 racemic trans-3-phenylglicidic acid methyl ester is reacted with ammonia to produce racemic erythro-3-phenylisoserine amide which is treated with a resolving agent such as tartaric, dibenzoyltartaric, lactic, mandelic or camphorsulphonic acid to give a mixture of diastereomeric salts. (2S,3S)-3-Phenylisoserine amide can be recovered in enantiomeric pure form after recrystallisation from suitable solvents. However, the C-2 stereogenic center is still in the S-configuration and further steps are necessary for inversion of configuration: the amino group must be protected with an acetyl moiety and the 2-OH group must be converted into its methanesulfonic derivative to provide an oxazoline compound, which is treated with HCl in ethanol to give the desired (2R,3S)-3-phenylisoserine acid methyl ester.
Therefore, there is still the need for an improved process for the preparation of (2R,3S)-3-phenylisoserine methyl ester which overcomes the above-mentioned drawbacks.